Obstructive Sleep Apnea Is Associated With Polycythemia in Men on Testosterone

Background: Polycythemia (erythrocytosis) is a known side effect of testosterone (T) replacement therapy (TRT) and appears to correlate with maximum T levels. There is also a well-established association between obstructive sleep apnea (OSA) and the development of polycythemia, which confers additional long-term cardiovascular morbidity. Synergy between TRT and OSA in the development of polycythemia remains poorly understood. Aim: The objective of this study was to retrospectively assess the relationship of OSA and secondary polycythemia in hypogonadal men receiving TRT. Methods: We performed a retrospective chart review of all men treated by a single provider from 2015 to 2019 for the diagnosis of hypogonadism. Patients who developed a hematocrit of 52% or greater were classified as having polycythemia. OSA was identified via clinical documentation or use of nocturnal continuous positive airway pressure. Demographics, laboratory values, treatment details, and comorbidities were recorded. Data were reported as mean +/- SD for parametric variables and median [interquartile range] for non-parametric values. Outcome: The primary outcome of this study was the association between OSA and polycythemia in hypogonadal men on TRT. Results: 474 men were included in this study. 62/474 (13.1%) men met the criteria for the diagnosis of polycythemia with a median hematocrit of 53.6 [interquartile range 52.6, 55.5]. Univariate analysis demonstrated a strong positive association between polycythemia and the concomitant diagnosis of OSA in hypogonadal men (P =.002). Even after correcting for age, body mass index (BMI), and peak T levels in the multivariate analysis (P =.01), this relationship remained significant with an odds ratio of 2.09 [95% CI 1.17, 3.76]. 37 men on TRT with polycythemia and OSA were included in the final cohort with a mean age of 59.2 +/- 11.4 years, mean BMI of 32.4 +/- 6.0, and median time from TRT initiation to polycythemia diagnosis of 3 years. All patients diagnosed with OSA were prescribed continuous positive airway pressure with poor compliance noted in 52.8% of men. 37.8% were managed via phlebotomy and 59.5% were managed via dose de-escalation of TRT. In hypogonadal men on TRT with polycythemia, BMI was the only risk factor strongly associated with OSA (P =.013). Clinical Translation: In hypogonadal men (particularly those with elevated BMI) on TRT who develop secondary polycythemia, a diagnosis of OSA should be strongly considered. Strengths & Limitations: This is a single provider retrospective study and further studies are needed to assess generalizability. Conclusions: In this retrospective single-center cohort, the development of polycythemia in hypogonadal men on TRT was associated with an increased prevalence of OSA.